Concentrated liquid acetic acid douche preparation containing aromatics



United States Patent 3 346 450 CONCENTRATED LIQIJID ACETIC ACID DOUCHE PREPARATION CONTAINING AROMATICS Galen F. Collins, Oscar L. Butt, and Buford Leroy Poet,

3,346,450 Patented Oct. 10, 1967 ICC possible irritations that may occur in the case of powder douche preparations due to the fact that all of the solid materials or oils are not in solution prior to use. Moreover a liquid preparation is easier to use since the product Bristol, Tenn, assignors to The S. E. Massengill Com- 5 g not ii slgmfica.nt lstlrnng for Preparailon pany Bristol, Tenn a corporation of Tennessee or use. A 1qu1d a so lends 1tse f to measuring devlces N0 Drawing Filed Jam 7 19 5 423,555 such as bottle caps which find better consumer acceptance.

3 Claims. (Cl. 16758) In spite of the advantages of liquid douche preparations they have not been as widely accepted as powder This invention in one of its aspects pertains to liquid douche products. One reason for this is believed to be douche compositions. In one of its more particular aspects that liquid douche preparations do not include the efiecthe invention relates to liquid douche compositions which, tive aromatics. Experience has shown that combinations although in aqueous phase, nevertheless contain aromatics. have excellent acceptance by users of powder douche The term aromatics as used in connection with douches products which contain menthol, oil of eucalyptus, methyl in powder form is well known and is understood to en- 5 salicylate and thymol, and various mixtures of these. compass one or more of menthol, thymol, oil of eucalyp- These aromatics have such low solubility in water they tus, methyl salicylate, and the like, all of which are virhave heretofore been used only in powders. Powder tually insoluble in water. See Modern Drug Encyclopedia douche preparations are highly diluted with water; this and Therapeutic Index, Drug Publications, Inc. permits solution of the aromatics.

A study of textbooks on gynecology reveals divergent 20 One possible method for incorporating aromatics in a views on douching. Some physicians advocate acid liquid douche preparation would be to dissolve the arodouches; some prefer alkaline douches; and there are matics in a water-soluble alcohol and dissolve this alcohol those who advocate no douching. It is generally believed, solution of aromatics in water. However in the case of however, that while many vaginal symptoms can be an acid douche, an alcohol-acid reaction is possible. Decleared up only by the removal of deep-seated causes, the sirable acid douches should provide a pH- between 3.5 therapeutic vaginal douche serves as an important adjuand 5 with good buffer capacity. The acid-alcohol reacvant in the treatment of such conditions. In addition a tion and accompanying ester formation will raise the pH surprising number of minor infections appear to be cured and reduce the buffer capacity of the douche preparation. by the use of acid douche preparations. It is therefore not possible to maintain the desired pH if It has been reported that alkaline douches have no a reaction occurs between the acidic material and the application in therapy of vaginitis. Vaginal therapy for alcohol. In addition esters introduce unexpected odors or Trichomonas vaginalis vaginitis depends upon the restoraa foreign substance undesirable from a psychological tion of the vaginal pH to a normal range of 3.5 to 5. standpoint.

Treatment for vaginalis vaginitis and for nonspecific vag- In accordance with one aspect of this invention it has initisconsists of acid douching. The selection of a suitbeen found that the combination of acetic acid and isoable douche is, therefore, a matter of great importance propyl alcohol can be used in a liquid douche preparation to the clinician. with essentially no reaction of alcohol with acid. An indi- T his invention is concerned with acid douche preparacation of the alcohol-acid reaction is the percent titratible tions used to restore and maintain an acid pH correspondacidity. This percent acidity is determined from cubic ing to that of the normal lactobacillary flora of the vagcentimeters of standard sodium hydroxide, titrating with inal tract. These are liquid preparations used as adjuncts 0.1 N sodium hydroxide using a phenolpht-halein end in the management of vaginal and cervical infections due point. The percent acidity decreases with increasing alcoto trichromonas and other vagino-cervicitis infections. hol-acid reaction. It would be expected that acetic acid There are certain advantages to the use of liquid douche would form esters with ethanol at about the same rate preparations for feminine hygiene. A liquid preparation as with isopropanol. The following data show that this is has all of the active ingredients dissolved. This eliminates not the case.

TABLE I.ESTERIFIOATION TEST Composition A Composition B Acetic Acid, gm 12. 5 Acetic Acid (glacial), gun--. 12. 5 Ethyl Alcohol 95%, ml 31. 5 I opropyl Alcohol 99%, ml-.. 41. 1 Sodium Hydroxide, gm 0.5 Isodium Hydroxide, gm... 0.5 Water, q.s., ml 100. 0 Water, q.S., ml 100,0 pH, approximately 3. 6 pH, approximately 3, 5

ACIDIIY Percent Acidity Ingredient Time Elapsed cm '40 c. I 0.

Composition:

Initial 12.33 A Acetic Acid in 30% Ethanol {1 month 11.91 10 92 9. 95 9 months 10.18 9.32 8 99 Initial 11.6 lrnonth 11.6 11.4 11.1 B Acetic Acidiu30% Isopro- 2months 11.4 11.2 11.0 panel. 3months 11.3 11.0 10.6 5months 11.2 10.8 10.5

The foregoing data show that in the case of acetic acid, commonly employed in douche preparations, there is a drop in the percent acidity at controlled room temperature (CRT) from 12.33 to 10.18 in 9 months with ethanol. With the composition of this invention using isopropyl alcohol there was virtually no change in five months. The percent acidity changed from 11.6 to only 11.2 at the end of five months. It can be seen, therefore, that very little reaction occurs between isopropyl alcohol and acetic acid. Such is not the case with ethyl alcohol and acetic acid. The use of this combination is hampered only by the odors of the materials which require adjustment in proportions of the various aromatics.

gredients will not change regardless of the quantity of alcohol, water or other ingredients added. The alcohol employed in the concentrated composition generally will be sufficient to dissolve the aromatics up to fifty percent of the water in the concentrate.

In the preparation of the douche compositions of this invention the aromatics can be dissolved in the isopropanol and the water-soluble ingredients dissolved in water. The two solutions are then combined. Another method is illustrated in the following example. In use, 10 ml. of the preparation is added to a quart (approximately 1000 ml.) of water. Accordingly, the examples herein are based on 10 ml. doses.

It has been pointed out that in addition to providing EXAMPLE A a pH of 3.5 to 5 an effective liquid douche should have Per 10 ml dose good buffer capacity. Buffer capacities can best be discussed in terms of the buffer index. Buffer index is the Acetic acid (glacial) mg 500 increment of base required to produce an increment in Sodium hydroxide mg the pH value of the solution. Buffer index as used herein Tartrazine RD. and C. Yellow No. 5 mg. 0.25 is the amount of standard sodium hydroxide, expressed 20 Quinoline yellow, water soluble D. and C. Yellow in millimoles, necessary to produce an increase from the No. 10 mg 1.50 original pH to pH 6.0. Isopropanol cc 4.0

Calculation: Buffer index: millimoles of NaOH=ml. Octylphenoxy polyethoxy ethanol Triton of NaOH addedxnormality of NaOH. X-l00 mg 150.0

TABLE II.BUFFER INDEX Buffer Index Ingredient Time Elapsed CRT 0. 1 50 0.

Composition:

Initial 20.15 A Acetic Acid in 30% Ethanol {1 month. 19. 33 17. 57 16. 12 9 months 16.34 14. 83 14.18 Initial 18.75 1 month. 18.73 19.15 19. 20 B Acetic Acid in 30% Isopro- 2 months... 18. 70 18.03 17. 65 panel. 3months 17.60 17.25 16.55 5rnonths 18.08 17.33 16.83

It can be seen from Table II that composition A does 1 omatlcs m 0.0 not have the bufier capac1ty WhlClJ. composition B of this 40 Water (is i 0 invention possesses. There is a marked drop in buffer n index in the tests conducted with composition A whereas 1 figgi f 5% there is little or no drop in buffer index in the case of h r 1o1 I t 1 composition B. i 8- Acetic acid lends itself admirably to concentrated llquld l e y a my a e douche preparations when isopropanol is employed as the 100.0

vehicle for the introduction of the aromatics. According to an aspect of this invention therefore, a liquid douche preparation containing aromatics is provided, which is water dilutable, to form an aqueous douche for restoring and maintaining a normal vaginal pH. The douche preparation is a buffered aqueous solution of acetic acid having a pH of 3.5 to 5. It contains (1) a surfactant or Wetting agent, and, (2) dissolved therein, an isopropyl alcohol solution of aromatics, the combination permitting solution with essentially no reaction of alcohol with acetic acid to raise the pH.

The douche preparation of this invention desirably is diluted 100 to 1000 parts to 1 by volume and will usually be sold with a device dispensing an amount to which a quart of water should be added. A douche preparation must, of course, not be harsh or irritating if used in stronger dilution since experience has shown that exact dilutions will not be used due to carelessness. The preparation of this invention can be so used.

This first aspect of the invention thus provides a liquid acetic acid douche preparation containing aromatics for use in the restoration of the vaginal pH to a normal range of 3.5 to 5, this aqueous douche composition containing 96 to 74 weight percent acetic acid as an active ingredient; 2 to 14 weight percent of a surfactant; and 2 to 12 weight percent aromatics, the total being 100 percent. The buffering is well known, sufiicient alkali being used to adjust the pH in the 3.5 to 5 range. Other ingredients such as known astringents, colorants and the like can, of course, be added. The percentages of the foregoing essential in- The acetic acid and sodium hydroxide are dissolved in half of the water (5 ml.). In the other half of the water the quinoline and tartrazine colorants are dissolved. The two 5 ml. moieties are then combined and the alcohol, Triton X- and aromatics are added to the solution. The composition can be filtered if necessary. When 10 ml. of the liquid is added to 1 quart of water, a pH of about 3.5 results with a surface tension of about 30 dynes. The solution has a buffer index of about 9. Sodium hydroxide is not a buffering agent as such, but when it reacts with acetic acid, it forms sodium acetate, and sodium acetateacetic acid is the buffering agent. Potassium hydroxide can be used as a replacement for the sodium hydroxide. In the formulation of Example A the No. 10 and N0. 5 colorants, the surfactant and the solution of aromatics are conventional. It is obvious that changes in these ingredients can be made without afiecting the therapeutic objective. Thus other colorants such as Rhodamine B Hydrochloride (D. and C. Red No. 19) and Brilliant Blue FCF (RD. and C. Blue No. 1) as well as other nonionic and anionic surfactants such as sodium lauryl sulfate, lauryl amide polyether, nonylphenoxy polyether ethanols and octylphenoxy polyether ethanols with three to thirty oxyethylene groups, and the like can be used. The sodium hydroxide, on the other hand, is used to provide the desired hydrogen ion concentration. Potassium hydroxide and other inorganic bases can be substituted therefor.

Douche preparations formulated according to the aspect of this invention which has been described are excellent for use by physicians. It is convenient and easy to use by both the physician and the patient. It maintains the normal vaginal pH. It has cleansing and antiseptic properties due to the surfactant. It is safe, and it contains the aromatics which experience has shown are in greater demand.

Many physicians, however, prefer that a douche preparation also have mild astringent properties, aluminum salts generally being employed. Boric acid and citric acid cannot be used in liquid preparations with aluminum salts, since both aluminum borate and aluminum citrate are relatively insoluble. In another of its aspects this invention provides a unique combination of astringents which overcome this solubility problem. In accordance with the practice of this aspect of the invention novel astringents have been found which in the combination produce the normal vaginal pH. This aspect of the invention contemplates the use of an aluminum chlorhydroxide complex wherein x is one to ten, and aluminum chloride in combination with acetic acid to provide a douche preparation with astringent properties. The following example illustrates the preparation of a liquid douche product of this aspect of the invention.

To make this douche preparation the water is separated into two moities. In one portion the acetic acid, aluminum chlorhydroxide complex, aluminum chloride, quinoline and tartrazine are dissolved in the amounts shown above for each 5 ml. quantity in the moiety. In the other moiety the alcohol, aromatics and surfactant are dissolved in the quantities shown per 5 ml. of moiety. A pH of 3.7 results.

Combinations of an aluminum chlorhydroxide complex and aluminum chloride have not, to our knowledge, been employed as astringents for the vaginal tract. In addition it was not realized that their use in combination with acetic acid would provide a composition possessing the buffer capacity of the douche preparation of this invention. When used in a weight ratio in the range of 1 aluminum chlorhydroxide complex:1.5 aluminum chloride:2 acetic acid, to 1 aluminum chlorhydroxide complex:2 aluminum chloride:3 acetic acid resulting in a pH of 3.5 to 5, a douche product with good bulfer capacity results. Using the foregoing ratios the ingredients are employed in ranges set forth hereinbefore. The aluminum chlorhydroxide complex and aluminum chloride are the buffer ingredients, constituting 1.5 to 20 percent of the composition.

Thus this invention provides not only a liquid douche preparation containing aromatics, but a liquid douche preparation containing new and unique astringents. All of the advantages of acid douches are attained by the preparations of the invention. Obviously changes in the other ingredients can be made. For example, several combinations of aromatics can be employed, and these can be varied depending on the alcohol employed. These and other obvious ramifications and variations are, of course, within the scope of this invention.

What is claimed is:

1. A concentrated liquid douche preparation containing aromatics, said preparation being water dilutable to form an aqueous douche for restoring and maintaining a normal vaginal pH, said preparation being a buffered aqueous solution of acetic acid having a pH of 3.5 to 5 and containing a wetting agent selected from the group consisting of sodium lauryl sulfate and nonionic surfactants, and, dissolved therein, an alcohol solution of aromatics selected from the group consisting of menthol, thymol, oil of eucalyptus, methyl salicylate and mixtures thereof, the alcohol permitting solution of the aromatics in the buffered aqueous acid solution, the alcohol being isopropanol, essentially no reaction of this alcohol with acetic acid occurring to raise the pH, the solution containing 96 to 74 weight percent acetic acid, 2 to 14 weight percent wetting agent, 2 to 12 weight percent aromatics, the total being 100 percent, and at least sufiicient alcohol to dissolve the aromatics.

2. The douche preparation of claim 1 wherein the wetting agent is an octylphenoxy polyether ethanol having three to thirty oxyethylene groups.

3. A concentrated douche preparation, said preparation water dilutable to form an aqueous douche for restoring and maintaining a normal vaginal pH, said preparation containing in aqueous solution 96 to 74 weight percent acetic acid as an active ingredient,

2 to 14 weight percent of a nonionic surfactant,

2 to 12 weight percent aromatics selected from the group consisting of menthol, thymol, oil of eucalyptus, methyl salicylate and mixtures thereof, the total being 100 percent,

aluminum chlorhydroxide and aluminum chloride as astringents and bulfer ingredients to maintain a pH of 3.5 to 5,

the weight ratio of aluminum chlorhydroxide to aluminum chloride to acetic acid being in the range of 1:1.5:2 to1:2:3, and

isopropanol,

the isopropanol having the aromatics dissolved therein permitting solution of the aromatics in the aqueous acetic acid solution with essentially no reaction with acetic acid raising the pH, the volume of isopropanol being sufiicient to dissolve the aromatics to 50 percent of the aqueous solution in volume.

References Cited UNITED STATES PATENTS 6/1951 Wright et a1 167-58 8/1953 Wright et a1. 16758 9/1959 Davis et .al. 167-58 3/1962 Hill 167-58 FOREIGN PATENTS 9/ 1962 France.

OTHER REFERENCES ALBERT T. MEYERS, Primary Examiner. JULIAN S. LEV'ITI, Examiner. VERA C. CLARKE, Assistant Examiner. 

1. A CONCENTRATED LIQUID DOUCHE PREPARTION CONTAINING AROMATICS, SAID PREPARTION BEING WATER DILUTABLE TO FORM AN AQUEOUS DOUCHE FOR RESTORING AND MAINTAINING A NORMAL VAGINAL PH, SAID PREPARATION BEING A BUFFERED AQUEOUS SOLUTION OF ACETIC ACID HAVING A PH OF 3.5 TO 5 AND CONTAINING A WETTING AGENT SELECTED FROM THE GROUP CONSISTING OF SODIUM LAURYL SULFATE AND NONIONIC SURFACTANTS, AND, DISSOLVED THEREIN, AN ALCOHOL SOLUTION OF AROMATICS SELECTED FROM THE GROUP CONSISTING OF MENTHOL, THYMOL, OIL OF EUCALYPTUS, MTHYL SALICYLATE AND MIXTURES THEREOF, THE ALCOHOL PERMITTING SOLUTION OF THE AROMATICS IN THE BUFFERED AQUEOUS ACID SOLUTION, THE ALCOHOL BEING ISOPROPANOL, ESSENTIALLY NO REACTION OF THIS ALCOHOL WITH ACETIC ACID OCCURRING TO RAISE THE PH, THE SOLUTION CONTAINING 96 TO 74 WEIGHT PERCENT ACETIC ACID, 2 TO 14 WEIGHT PERCENT WETTING AGENT, 2 TO 12 WEIGHT PERCENT AROMATICS, THE TOTAL BEING 100 PERCENT, AND AT LEAST SUFFICIENT ALCOHOL TO DISSOLVE THE AROMATICS. 